A novel anoikis-related gene signature identifies LYPD1 as a novel therapy target for bladder cancer.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Urinary Bladder Neoplasms*/genetics ; Matrix Attachment Region Binding Proteins*; Humans ; Anoikis/genetics ; Genes, Homeobox ; Urinary Bladder ; Nomograms ; Prognosis

Bladder cancer (BLCA) is a malignant tumor associated with unfavorable outcomes. Studies suggest that anoikis plays a crucial role in tumor progression and cancer cell metastasis. However, its specific role in bladder cancer remains poorly understood. Our objective was to identify anoikis-related genes (ARGs) and subsequently construct a risk model to assess their potential for predicting the prognosis of bladder cancer.The transcriptome data and clinical data of BLCA patients were sourced from The Cancer Genome Atlas and GEO database. We then performed the differential expression analysis to screen differentially expressed ARGs. Subsequently, we conducted non-negative matrix factorization (NMF) clustering analysis to establish molecular subtypes based on the differentially expressed ARGs. The CIBERSORT algorithm was used to estimate the quantification of different cell infiltration in BLCA tumor microenviroment. A prognostic risk model containing 7 ARGs was established using Lasso-Cox regression analysis. The nomogram was built for predicting the survival probability of BLCA patients. To determine the drug sensitivity of each sample from the high- and low-risk groups, the R package "pRRophetic" was performed. Finally, the role of LYPD1 was explored in BLCA cell lines.We identified 90 differential expression ARGs and NMF clustering categorizated the BLCA patientss into two distinct groups (cluster A and B). Patients in cluster A had a better prognosis than those in cluster B. Then, we established a ARGs risk model including CALR, FASN, FOSL1, JUN, LYPD1, MST1R, and SATB1, which was validated in the train and test set. The results suggested overall survival rate was much higher in low risk group than high risk group. The cox regression analysis, ROC curve analysis, and nomogram collectively demonstrated that the risk model served as an independent prognostic factor. The high risk group had a higher level TME scores compared to the low risk group. Furthermore, LYPD1 was low expression in BLCA cells and overexpression of LYPD1 inhibits the prolifearation, migration and invasion.In the current study, we have identified differential expression ARGs and constructed a risk model with the promise for guiding prognostic predictions and provided a therapeutic target for patients with BLCA.
(© 2024. The Author(s).)

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202310511 Health Commission of Jiangxi Province; SKJP_220212063 Health Commission of Jiangxi Province; 82260598 the National Nature Science Foundation of China; 20225BCJ22009 Jiangxi Provincial academic and technical leaders training program

0 (SATB1 protein, human)
0 (Matrix Attachment Region Binding Proteins)

Date Created: 20240208 Date Completed: 20240214 Latest Revision: 20240214

20240214

PMC10853254

10.1038/s41598-024-53272-0

38332160